Miler Eliana A, Ríos de Molina María Del Carmen, Domínguez Gabriela, Guerra Liliana N
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Redox Rep. 2008;13(4):185-91. doi: 10.1179/135100008X308920.
We have already demonstrated that a combined treatment of methimazole and an antioxidant mixture improved the condition of hyperthyroid patients both biochemically and clinically. Elevated thyroid hormone levels might trigger signs and symptoms of hyperthyroidism through the increase of free radicals. To study the direct effect of thyroid hormone on cellular markers of oxidative stress, we carried out in vitro assays in which 0.1-20.0 nM T3 (6.5-1300.0 ng/dl) doses were added to culture media of the human hepatocyte cell line Hep G2 for 1-24 h. T3 increased malondialdehyde (MDA) and intracellular oxidized glutathione (GSSG) levels; SOD activity was also higher with hormone treatment, whereas catalase and glutathione peroxidase activities showed no variation at different T3 doses and during all experimental times. When ascorbic acid was added to the culture, the MDA level decreased and SOD activity was increased. With higher doses of T3 (e.g. 200 nM), cell death occurred (69% of apoptotic cells). The increase in SOD activity was not enough to overcome the effect of T3 since MDA and GSSG remained high during a 24-h experiment. We showed a beneficial effect of ascorbic acid when cells were exposed to a T3 dose of 20 nM, a higher level of hormone than that achieved in hyperthyroidism.
我们已经证明，甲巯咪唑和抗氧化剂混合物联合治疗可在生化和临床方面改善甲状腺功能亢进患者的病情。甲状腺激素水平升高可能通过自由基增加引发甲状腺功能亢进的体征和症状。为了研究甲状腺激素对氧化应激细胞标志物的直接影响，我们进行了体外试验，向人肝细胞系Hep G2的培养基中添加0.1 - 20.0 nM T3（6.5 - 1300.0 ng/dl）剂量，作用1 - 24小时。T3增加了丙二醛（MDA）和细胞内氧化型谷胱甘肽（GSSG）水平；激素处理后超氧化物歧化酶（SOD）活性也更高，而过氧化氢酶和谷胱甘肽过氧化物酶活性在不同T3剂量和所有实验时间内均无变化。当向培养物中添加抗坏血酸时，MDA水平降低，SOD活性增加。使用较高剂量的T3（例如200 nM）时，细胞死亡发生（69%为凋亡细胞）。SOD活性的增加不足以克服T3的影响，因为在24小时实验期间MDA和GSSG仍保持较高水平。当细胞暴露于20 nM的T3剂量（高于甲状腺功能亢进时达到的激素水平）时，我们显示了抗坏血酸的有益作用。
